In cerebrospinal fluid, acetylcholinesterase activity and somatostatin and neuropeptide Y concentrations did not differ from control values in either young or old Down syndrome patients. Analysis of lumbar cerebrospinal fluid fractions in healthy young and old subjects indicated no anterior-posterior gradients for somatostatin and neuropeptide Y, but higher acetylcholinesterase in caudal as compared to rostral fractions in younger subjects, indicative of sources for this enzyme from the spinal cord. Acetylcholinesterase gradients in cerebrospinal fluid were absent in old healthy subjects, who had higher mean activity overall. CSF production rates and caudorostral gradients of CSF protein were normal in DS adults. Cerebrospinal fluid and plasma myo-inositol levels in Down's syndrome patients were determined by a newly developed mass spectrometric assay. Myo-inositol levels in cerebrospinal fluid in Down's syndrome were increased significantly compared to normals.